The antiproliferative effect of HGF on hepatoma cells involves induction of apoptosis with increase in intracellular polyamine concentration levels.
Hepatocyte growth factor (HGF) induced apoptosis and decreased the DNA synthesis in Hep G2 cells. In the HGF group interleukin-1 converting enzyme, ornithine decarboxylase (ODC) activity and intracellular polyamine concentrations were increased compared to those of the control group. Administration of the ODC inhibitor decreased polyamine concentration, and inhibited apoptotic changes in the cells. These changes were reversed by exogenous addition of polyamine. These findings suggest that one of the mechanisms by which HGF exerts its antiproliferative effect is induction of apoptosis and that increase in intracellular polyamine concentration may be one of the triggers of cell death.
Yanagawa
K
K
First Department of Surgery, Osaka City University, Medical School, 1-5-7 Asahimachi, Abenoku, Osaka 545, Japan.
Yamashita
T
T
Yada
K
K
Ohira
M
M
Ishikawa
T
T
Yano
Y
Y
Otani
S
S
Sowa
M
M
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D020170:Caspase 1; D003546:Cysteine Endopeptidases / Q000378:metabolism; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000096:biosynthesis; D000518:Eflornithine / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms / Q000473:pathology*; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism*; D011700:Putrescine / Q000494:pharmacology; D013095:Spermidine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D011073:Polyamines; D017228:Hepatocyte Growth Factor; D003546:Cysteine Endopeptidases; D020170:Caspase 1; D009955:Ornithine Decarboxylase; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine